Evidence map›Paper›PMID 30027104›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2018

Cladribine tablets added to IFN-β in active relapsing MS: The ONWARD study.

Xavier Montalban, Thomas P Leist, Bruce A Cohen, Harold Moses, Jackie Campbell, Christine Hicking, Fernando Dangond

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00436826 (A Phase II, Multicenter, Randomized, Double Blind, Placebo Controlled, Safety, Tolerability and Efficacy Study of Add-on Cladribine Tablet Therapy With Interferon-beta), which is not on this map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
5.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00436826 phase2completednot on this map

A Phase II, Multicenter, Randomized, Double Blind, Placebo Controlled, Safety, Tolerability and Efficacy Study of Add-on Cladribine Tablet Therapy With Interferon-beta (IFN-β) Treatment in Multiple Sclerosis Subjects With Active Disease

TypeinterventionalSponsorEMD Serono Research & Development Institute, Inc.Ran2006 to 2012Enrolled172ConditionsMultiple SclerosisArmsCladribine, Placebo, Interferon-beta (IFN-beta)
3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Cladribine tablets in the new multiple sclerosis era.Therapeutic advances in neurological disorders · 2025
    Review
  5. Review
  6. Article
  7. Article
  8. Updates and advances in multiple sclerosis neurotherapeutics.Neurodegenerative disease management · 2023
    Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Skin Reactions in Patients With Multiple Sclerosis Receiving Cladribine Treatment.Neurology(R) neuroimmunology & neuroinflammation · 2021
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 5 countries.

Xavier MontalbanDepartment of Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Center of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Department of Neurology (X.M.), St. Michael's Hospital, University of Toronto, Ontario, Canada; Division of Clinical Neuroimmunology (T.P.L.), Jefferson University, Comprehensive MS Center, Philadelphia, PA; Department of Neurology (B.A.C.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Neurology (H.M.), Vanderbilt University Medical Center, Nashville, TN; inScience Communications (J.C.), Springer Healthcare, Chester, United Kingdom; Research and Development Global BioStatistics (C.H.), Merck KGaA, Darmstadt, Germany; and Global Clinical Development Center (F.D.), EMD Serono Inc., Billerica, MA.
Thomas P LeistDepartment of Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Center of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Department of Neurology (X.M.), St. Michael's Hospital, University of Toronto, Ontario, Canada; Division of Clinical Neuroimmunology (T.P.L.), Jefferson University, Comprehensive MS Center, Philadelphia, PA; Department of Neurology (B.A.C.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Neurology (H.M.), Vanderbilt University Medical Center, Nashville, TN; inScience Communications (J.C.), Springer Healthcare, Chester, United Kingdom; Research and Development Global BioStatistics (C.H.), Merck KGaA, Darmstadt, Germany; and Global Clinical Development Center (F.D.), EMD Serono Inc., Billerica, MA.
Bruce A CohenDepartment of Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Center of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Department of Neurology (X.M.), St. Michael's Hospital, University of Toronto, Ontario, Canada; Division of Clinical Neuroimmunology (T.P.L.), Jefferson University, Comprehensive MS Center, Philadelphia, PA; Department of Neurology (B.A.C.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Neurology (H.M.), Vanderbilt University Medical Center, Nashville, TN; inScience Communications (J.C.), Springer Healthcare, Chester, United Kingdom; Research and Development Global BioStatistics (C.H.), Merck KGaA, Darmstadt, Germany; and Global Clinical Development Center (F.D.), EMD Serono Inc., Billerica, MA.
Harold MosesDepartment of Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Center of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Department of Neurology (X.M.), St. Michael's Hospital, University of Toronto, Ontario, Canada; Division of Clinical Neuroimmunology (T.P.L.), Jefferson University, Comprehensive MS Center, Philadelphia, PA; Department of Neurology (B.A.C.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Neurology (H.M.), Vanderbilt University Medical Center, Nashville, TN; inScience Communications (J.C.), Springer Healthcare, Chester, United Kingdom; Research and Development Global BioStatistics (C.H.), Merck KGaA, Darmstadt, Germany; and Global Clinical Development Center (F.D.), EMD Serono Inc., Billerica, MA.
Jackie CampbellDepartment of Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Center of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Department of Neurology (X.M.), St. Michael's Hospital, University of Toronto, Ontario, Canada; Division of Clinical Neuroimmunology (T.P.L.), Jefferson University, Comprehensive MS Center, Philadelphia, PA; Department of Neurology (B.A.C.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Neurology (H.M.), Vanderbilt University Medical Center, Nashville, TN; inScience Communications (J.C.), Springer Healthcare, Chester, United Kingdom; Research and Development Global BioStatistics (C.H.), Merck KGaA, Darmstadt, Germany; and Global Clinical Development Center (F.D.), EMD Serono Inc., Billerica, MA.
Christine HickingDepartment of Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Center of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Department of Neurology (X.M.), St. Michael's Hospital, University of Toronto, Ontario, Canada; Division of Clinical Neuroimmunology (T.P.L.), Jefferson University, Comprehensive MS Center, Philadelphia, PA; Department of Neurology (B.A.C.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Neurology (H.M.), Vanderbilt University Medical Center, Nashville, TN; inScience Communications (J.C.), Springer Healthcare, Chester, United Kingdom; Research and Development Global BioStatistics (C.H.), Merck KGaA, Darmstadt, Germany; and Global Clinical Development Center (F.D.), EMD Serono Inc., Billerica, MA.
Fernando DangondDepartment of Neurology-Neuroimmunology (X.M.), Multiple Sclerosis Center of Catalonia (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain; Department of Neurology (X.M.), St. Michael's Hospital, University of Toronto, Ontario, Canada; Division of Clinical Neuroimmunology (T.P.L.), Jefferson University, Comprehensive MS Center, Philadelphia, PA; Department of Neurology (B.A.C.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Neurology (H.M.), Vanderbilt University Medical Center, Nashville, TN; inScience Communications (J.C.), Springer Healthcare, Chester, United Kingdom; Research and Development Global BioStatistics (C.H.), Merck KGaA, Darmstadt, Germany; and Global Clinical Development Center (F.D.), EMD Serono Inc., Billerica, MA.
Northwestern University · USVall d'Hebron Hospital Universitari · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo evaluate the safety and efficacy of cladribine tablets in patients still experiencing active relapsing MS despite interferon (IFN)-β treatment.

methodsA 96-week phase II study, randomizing patients treated with IFN-β to cladribine tablets 3.5 mg/kg/IFN-β or placebo/IFN-β. Patients were to receive cladribine tablets 3.5 mg/kg/IFN-β or placebo/IFN-β in a 2:1 ratio (n = 172) with safety and exploratory efficacy outcomes being assessed.

resultsAdverse events (AEs) and serious AEs were similar across treatment groups, except lymphopenia. Fifty of 124 (40.3%) cladribine/IFN-β recipients vs 0% of placebo/IFN-β recipients reported lymphopenia as an AE, with grade 3/4 lymphopenia (laboratory lymphocyte count < 500 cells/mm

conclusionsIn patients with active relapsing MS despite IFN-β treatment, cladribine tablets 3.5 mg/kg/IFN-β reduced relapses and MRI lesion activity over 96 weeks compared with placebo/IFN-β but led to an increased incidence of lymphopenia. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with active relapsing MS despite IFN-β treatment, cladribine tablets added to IFN-β reduced relapses and MRI lesion activity over 96 weeks and increased the incidence of lymphopenia. CLINICAL

trial registrationNCT00436826.

Identifiers

PMID30027104
PMCPMC6047834
OpenAlexW2869377759

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.